The flash-electropolishing of focused ion beam samples for V-4Cr-4Ti alloys is established, and the microstructures of high-purity V-4Cr-4Ti alloys after He ion irradiation are examined by transmission electron microscopy from room temperature to 700°C. The correlation between irradiation hardening behavior and microstructural changes is clarified. During room temperature irradiation, defect clusters are formed at shallow positions in the specimens and no He bubbles are observed at the damage peak position. In contrast, 500 and 700°C, TiCON precipitates are predominantly formed and He bubbles and voids were formed at the damage peak position. The results of nanoindentation tests and a comparison of irradiation hardening by irradiation damage indicate that the obstacle barrier strength factorαof TiCON is 0.45 while that of the irradiation defect clusters irradiated at room temperature is 0.10. Irradiation damage in the He ion range extends toward the interior of the specimens with increasing irradiation temperature.